Various illnesses and disorders lead to situations that require continuous and tight control of systemic metabolic processes. As a result of the disease state it is difficult to control or predict the vast reaching systemic metabolic processes involved, where it is particularly difficult to predict the affects of one aspect of disease state on other aspects. However, such control is sought after to ensure the proper functioning of the body in all its systems.
Diabetes is perhaps the most well known illness that requires such close control of a systemic metabolic process. Control of diabetes and in particular the balance between blood sugar and insulin levels has far reaching and often lethal consequences if such control is lost. Systemic metabolic control for individuals suffering from diabetes has improved over the years with increased awareness, various systems and close monitoring of blood glucose levels, automatic drug delivery pumps and similar analyte and drug delivery systems that have been developed. However the systemic solutions such as an electronic artificial pancreas or close looped diabetes control system continues to elude us as a single point solution has yet to be found, particularly because of the human factors involved in control of the metabolic process involved with diabetes.
Furthermore such an automatic close loop system is only available to a small portion of the diabetic population. Such system is not available to the majority of diabetics primarily due to the cost involved in such a system. Most diabetics use syringe and/or injection pen based drug delivery systems for both basal and/or bolus insulin drug delivery.
There are many known metabolic processes having effect on diabetics include for example food intake, exercise, sleep, cardiovascular system, blood pressure, and involve both intrinsic biological processes, anatomical disposition, and human behavioral factors, a combination of factors that are not readily controllable, even if a closed loop system is available.
In many instances, diabetics require insulin injection around the clock to maintain proper blood glucose levels. Two major types of insulin may be administered—“long acting” insulin, that provides the basal insulin rate needed for keeping the blood glucose levels in the desired range for stretches of time for example, between meals and overnight and sometimes throughout a single day, a number of days or even a week. The basal, “slow acting”, type of insulin does not have to rapidly reach the patient's circulatory system in order to take effect. The second type of insulin, is a short “rapid-acting”, “bolus”, insulin that is injected in relation to caloric intake or a meal and provides an amount of insulin for matching a dose of carbohydrates consumed by the patient. As its name suggests, “fast acting” insulin generally needs to reach the metabolic system quickly in order to take part in the metabolic process in a timely fashion, so as to avoid unwanted extreme situations.
When a patient consumes food, his or her levels of glucose rises which requires a metabolic reaction to offset the glucose rise, in diabetics this is achieved by administrating insulin, so as to maintain homeostasis or balance of blood glucose levels. The vast majority of the diabetic population utilized syringe based drug delivery devices to administer insulin so as to maintain blood glucose homeostasis. Unfortunately, existing “rapid acting” insulin currently in use with many conventional subcutaneous injection devices, including injection-ports, are incapable of quickly matching or preventing the rise of blood glucose, leading to metabolic imbalance due to lack of matching. Similarly, delay in such matching may also be experienced when “rapid-acting” insulin is administered.
Some of the reasons for this delay include a lag in the absorption of insulin from the injection site and the time it takes for complex insulin molecules to break down into monomers.
Additionally, since blood glucose levels rise shortly following the meal, the delay in matching insulin to the rising levels causes post-prandial hyperglycemic events (i.e., when levels of blood glucose are above normal) to occur. Further, occasionally after a certain period of time passes (e.g., 2-3 hours) after a meal, the blood glucose levels drop while the administered meal-time insulin concentration in the blood is rising, followed by the peak of the systemic insulin effect and may result in causing hypoglycemic events (i.e., when levels of blood glucose are below normal) to occur. Both hyperglycemic and hypoglycemic events are highly undesirable, and are indicative of a metabolic mismatch or imbalance in the systemic metabolic processes.
Other factors taking effect in the systemic metabolic process, include blood perfusion. Particularly local blood perfusion at the insulin injection region/site shows large variability, from one site to the other. Amongst other parameters, an important factor affecting blood perfusion includes ambient temperature. Ambient temperature is believed to be an important factor in the large variations to the delay of the peak of time profile of the insulin action. Such variations in the insulin peak action period further increase the variability in the blood glucose level, leading to metabolic imbalance.
Other factors that play into the systemic metabolic process include local affects at the injection site. For example, it is known that certain drugs including insulin are growth hormones. These drugs when injected several times at the same location can cause local cell growth, causing Lipohypertrophy. Therefore continuous insulin injection at a single injection site for extended period of time, for example several times per day or over several days, may lead to Lipohypertrophy. Increased local blood perfusion at the injection site to promote drug uptake to the circulatory system may reduce unwanted Lipohypertrophy of the injection site.
Other factors having a marked affect on the systemic metabolic process of diabetics include diet and/or food intake and level of exercise. Both factors have great affect on the systemic metabolic process and contribute greatly to the type of insulin to delivery, the required insulin dose, blood perfusion and likelihood of experiencing hyperglycemic and/or hypoglycemic events.
To date, despite numerous advances in the type of insulin drugs available to diabetics, continuous glucose monitoring devices, automatic drug delivery systems and pumps, closed looped monitoring, the sought after balance in the systemic metabolic control eludes many diabetics. This is largely believed to be a direct result of individual human factors, such as incorrect dosage, wrong drug type, inappropriate care of the drug itself (exposure), inactivity, unpredictable eating habits, and the like, are largely unpredictable.
Most insulin treated diabetics use injection and/or syringe based devices on a daily basis, they sometime use more than just one injection device to administer their insulin dose, even a single dose. They can and often use more than one blood glucose meter to measure their blood glucose levels before administering insulin. While there are new developments directed to capture daily diabetic behavior and parameters which can be used to optimize treatment, this human behavior is largely unpredictable, makes it difficult to track all the devices that are used by patients on a daily basis.
Therefore due to the non-predictable nature of the human factor and its involvement in the systemic metabolic process governing diabetes a different approach is required that will offset or attempt to offset at least some of the human factors involved, to try to maintain a blood glucose balance.